Effective treatment of adjuvant arthritis with a stimulatory CD28-specific monoclonal antibody

J Rheumatol. 2006 Jan;33(1):110-8.


Objective: To determine the immunomodulatory effects of the anti-rat CD28 monoclonal antibody (Mab) JJ316 on the onset of rat adjuvant arthritis (AA). JJ316 is a superagonistic Mab that induces polyclonal T cell proliferation in the absence of T cell receptor (TCR) ligation and promotes the expansion of regulatory T cells.

Methods: Female Wistar rats in which AA was induced were treated with JJ316 on Day 0 and Day 9 postinduction. A parallel treatment with JJ319, a "conventional" CD28-specific Mab that costimulates anti-TCR triggered proliferation, was performed. Severity of arthritis was monitored by means of an arthritic score, and by recording hindpaw volume and body weight increases. Serum antibodies against the AA-inducing mycobacteria were also determined by ELISA. To ascertain the effect of JJ316 on T lymphocytes in vivo, blood CD4+CD45RChigh (Th1-like) and CD4+CD45RClow (Th2-like) cells were analyzed by flow cytometry, and the relative levels of interleukin 2 (IL-2), IL-10, and interferon-g (IFN-g) mRNA in synovial tissue were measured by real-time reverse transcription-polymerase chain reaction.

Results: JJ316 efficiently prevented the inflammatory process of AA. This effect was associated with a specific decrease in the blood CD4+CD45RChigh/CD4+CD45RClow T cell ratio and high IL-10 mRNA expression in the synovia. In addition, anti-mycobacteria antibody levels decreased in JJ316 treated animals. In contrast, administration of the conventional anti-CD28 Mab JJ319 did not improve inflammation.

Conclusion: JJ316, a stimulatory CD28-specific Mab known to promote Th2 function and the expansion of regulatory T cells, provides effective protection from AA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bacterial / blood
  • Antibodies, Monoclonal / therapeutic use*
  • Antigens, Bacterial / immunology
  • Arthritis, Experimental / immunology
  • Arthritis, Experimental / pathology
  • Arthritis, Experimental / therapy*
  • CD28 Antigens / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology
  • Cell Count
  • Cytokines / genetics
  • Cytokines / metabolism
  • Female
  • Hindlimb / drug effects
  • Hindlimb / pathology
  • Immunologic Factors / therapeutic use*
  • Mycobacterium / immunology
  • RNA, Messenger / analysis
  • Rats
  • Rats, Wistar
  • Synovial Membrane / drug effects
  • Synovial Membrane / metabolism
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / pathology


  • Antibodies, Bacterial
  • Antibodies, Monoclonal
  • Antigens, Bacterial
  • CD28 Antigens
  • Cytokines
  • Immunologic Factors
  • RNA, Messenger